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Old 01-07-2012, 10:33 PM   #1
Lani
Senior Member
 
Join Date: Mar 2006
Posts: 4,778
progress being made on new treatment for her2+ bone mets

radionuclide-herceptin conjugate ( a radionuclide-rituxin conjugate is already on the market for lymphoma--rituxin is another monoclonal antibody)
They attach a radioactive element to herceptin and voila-- a miniature radiation emitter targetted to her2+ breast cancer cells. This one homes to bone(or its daughter nuclide does)


EJNMMI Res. 2011 Aug 24;1(1):18.
Experimental α-particle radioimmunotherapy of breast cancer using 227Th-labeled p-benzyl-DOTA-trastuzumab.
Abbas N, Heyerdahl H, Bruland OS, Borrebæk J, Nesland J, Dahle J.
Source
Department of Radiation Biology, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway. nasir.abbas@rr-research.no.
Abstract
ABSTRACT:
BACKGROUND:
The aim of the present study was to explore the biodistribution, normal tissue toxicity, and therapeutic efficacy of the internalizing low-dose rate alpha-particle-emitting radioimmunoconjugate 227Th-trastuzumab in mice with HER2-expressing breast cancer xenografts.
METHODS:
Biodistribution of 227Th-trastuzumab and 227Th-rituximab in nude mice bearing SKBR-3 xenografts were determined at different time points after injection. Tumor growth was measured after administration of 227Th-trastuzumab, 227Th-rituximab, cold trastuzumab, and saline. The toxicity of 227Th-trastuzumab was evaluated by measurements of body weight, blood cell, and clinical chemistry parameters, as well as histological examination of tissue specimens.
RESULTS:
The tumor uptake reached peak levels of 34% ID/g (4.6 kBq/g) 3 days after injection of 400 kBq/kg of 227Th-trastuzumab. The absorbed radiation dose to tumor was 2.9 Gy, while it was 2.4 Gy to femur due to uptake of the daughter nuclide 223Ra in bone; the latter already explored in clinical phases I and II trials without serious toxicity. A significant dose-dependent antitumor effect was observed for dosages of 200, 400, and 600 kBq/kg of 227Th-trastuzumab but no effect of 400 and 600 kBq/kg 227Th-rituximab (non-tumor binding). No serious delayed bone marrow or normal organ toxicity was observed, but there was a statistical significant reduction in blood cell parameters for the highest-dose group of 227Th-trastuzumab treatment.
CONCLUSION:
Internalizing 227Th-trastuzumab therapy was well tolerated and resulted in a dose-dependent inhibition of breast cancer xenograft growth. These results warrant further preclinical studies aiming at a clinical trial in breast cancer patients with metastases to bone.
PMID: 22214432 [PubMed - in process]
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